The study of autoimmunity and disease continues with an emphasis on type 1 diabetes mellitus. The antigen which was recognized by an autoantibody, found in a small percentage of patients with type 1 diabetes, is chymotrypsin, or a "chymotrypsin-like" protein, as determined by amino acid partial sequence analysis and amino acid composition analysis. Affinity column preabsorption of antibodies raised against chymotrypsin delineated two antibody populations. With immunofluorescence microscopy, one population of antibody reacted with the monkey exocrine pancreas while the other reacted with the islets of langerhans. Western immunoblot analysis of the two populations revealed that the antibodies reacting with the exocrine pancreas recognized chymotrypsin or the "chymotrypsin like" protein, while the population reacting with the islets reacted with a tri-isomeric, soluable protein with pI's ranging from 6.8-7.0. This protein was purified, but amino acid sequence analysis of it has so far been blocked. Antibody formation against this protein and new attempts, after partial digestion, to sequence this protein are in progress. The possibility that an idiotypic/anti-idiotypic relationship between the two populations of antibodies has been raised. Functional assays to test this possibility are in progress.